The long term objective of this application is to provide instrumentation to establish a facility for automated DNA sequencing, oligonulceotide synthesis, and other DNA manipulations at Washington University. This equipment will facilitate the research of the 13 primary applicants as well as other researchers at Washington University who may wish to use these technologies in the future. The research projects of the 13 applicants are diverse and encompass many health-related subjects, including bacterial pathogenesis, transcription regulation, cellular differentiation and development, and evolutionary genetics. The Integrated DNA Chemistry Facility within the Department of Biology at Washington University will serve as a shared facility to provide primary functions of automated DNA sequencing, oligonucleotide synthesis and DNA isolation and purification. Recent advances in technology for these procedures, particularly the advent of automated instrumentation for DNA sequencing and oligonucleotide synthesis, have created a problem for many laboratories that can not individually justify acquisition of the instruments. The goal of the facility will be efficient use by the maximum number of participating scientists of instrumentation that can not be afforded in individual laboratories. Funds are requested to purchase (i) an oligonucleotide synthesizer, (ii) an automated DNA sequencer, (iii) and HPLC system, (iv) an uninterruptible power supply for these instruments, (v) an ultracentrifuge, (vi) a lyophilizer, and (vii) a scintillation counter. The Department will provide other essential equipment, including a high-speed refrigerated centrifuge and film processor, renovate ca. 500 square feet for the facility, and hard wire interfaces to the Department's Digital Equipment Corporation Vax computer network. This facility will be supervised by Dr. Robert Landick, overseen by a user committee, and run by a full-time research assistant. Use by graduate students, postdoctorals, and faculty will be scheduled so as to make maximum use of the equipment to potentiate research progress by all participants.